Molecular genetics of retinitis pigmentosa in two Romani (Gypsy) families.

PURPOSE: To identify the disease-causing mutations in two large Bulgarian Romani (Gypsy) pedigrees: one with autosomal dominant retinitis pigmentosa (adRP) with partial penetrance and the other with severe X-linked RP (xlRP). METHODS: Detailed clinical investigations were undertaken and genomic DNA was extracted from blood samples. DNA was analyzed by PCR amplification with gene-specific primers and direct genomic sequencing. RESULTS: Analysis of the complete coding sequence of PRPF31 in the adRP family led to the identification of a new heterozygous splice site mutation IVS6+1G>T. RPGR mutation screening in affected male individuals in the X-linked RP family identified a hemizygous c.ORF15+652_653delAG mutation. Interestingly this mutation was found in a homozygous state in one severely affected female from the family. CONCLUSIONS: In this first report of molecular genetic analysis of retinitis pigmentosa in Romani families, we describe a novel PRPF31 mutation and present the first case of a homozygous mutation in the RPGR gene in a female individual.

A new locus (RP31) for autosomal dominant retinitis pigmentosa maps to chromosome 9p.

Retinitis pigmentosa (RP) is a debilitating disease of the retina affecting approximately 1.5 million people worldwide. RP shows remarkable heterogeneity both clinically and genetically, with more than 40 genetic loci implicated, 12 of which account for the autosomal dominant form (adRP) of inheritance. We have recently identified a French Canadian family that presents with early onset adRP. After exclusion of all known loci for adRP, a genome-wide search established firm linkage with a marker from the short arm of chromosome 9 (LOD score of 6.3 at recombination fraction theta=0). The linked region is flanked by markers D9S285 and D9S1874, corresponding to a genetic distance of 31 cM, in the region 9p22-p13.